antinucleosome

In the last few years, several reports have shown that chromatin (nucleosome) represents the main autoantigen-immunogen in systemic lupus erythematosus (SLE) and that specific antibodies are an important marker of the disease. To verify the clinical sensitivity and specificity of antinucleosome autoantibodies (ANuAs), we evaluated three ELISA immunoassay methods using different autoantigen preparations: Quanta Lite Chromatin, Medizym Anti-nucleo, and Nucleosome IgG Elisa. We compared the results with those obtained using two ELISA assays for determining anti-native DNA (anti-nDNA) antibodies: Axis-Shield and EliA dsDNA...

We have analysed the clinical features and autoantibody profile of 84 tunisian patients with newly diagnosed systemic lupus erythematosus (SLE). Antinuclear antibodies (ANA) were detected by an immunofluorescence method, anti-dsDNA and anti-cardiolipin (aCL) antibodies by ELISA, antinucleosome and anti-extractible nuclear antigens (or anti-ENA: anti-Sm, anti-RNP, anti-SSA and anti-SSB) by immunodot. The mean age of the patients was 29,9 years and the sex-ratio F/M was 6. The most common initial features were haematological (80%), rheumatological (78%) and cutaneous (75%) disorders...

The aim of this study was to investigate the clinical significance of antinucleosome antibodies in Tunisian systemic lupus erythematosus (SLE) patients. IgG antinucleosome antibodies were detected by a qualitative enzyme immunoassay (immunodot) in the sera of SLE patients at onset of disease. The patients were divided into two groups according to the result of the antinucleosome antibodies test: positive (group A) and negative (group B). The two groups were also evaluated for clinical and biological parameters...

Nucleosomes are the dominant autoantigens in patients with systemic lupus erythematosus (SLE), and immune complexes involving nucleosomes are the major cause of tissue damage. The activity of DNase I, the enzyme responsible for nucleosome degradation, has been found to be decreased in patients with SLE. However, it is not known whether DNase activity is a clinically useful parameter. The aim of our study was to assess DNase activity in a prospective study of 113 patients with SLE in relation to disease activity and organ involvement...

BACKGROUND: Localized scleroderma (LSc) exhibits autoimmunity, and antihistone antibody is frequently detected. The major antigens recognized by antihistone antibody are histones H1, H2A and H2B, which are located on the outer side of the nucleosome and are relatively more accessible for antibody binding. Therefore, it has been hypothesized that antihistone antibody is induced by nucleosome or native chromatin as immunogens in LSc. OBJECTIVES: To determine whether antinucleosome antibody is present in patients with LSc...

The specific modification of autoantigens and their redistribution into blebs at the surface of apoptotic cells contribute to the induction of autoimmune responses. Blebs containing fragments of the apoptotic nucleus separate from the remainder of the cell to form membrane-bound sub-cellular particles (SCPs), otherwise known as apoptotic bodies. To determine whether apoptotic bodies containing nuclear antigens represent a defined subset of SCPs, we examined the heterogeneity of particles generated by Jurkat cells following synchronization of the cell cycle by serum withdrawal and inhibition of topoisomerase I by camptothecin...

Systemic lupus erythematosus (SLE) is characterized by the development of a large array of autoantibodies that primarily are directed against the whole chromatin (antinucleosome) and its individual components, dsDNA and histones. Apoptotic defects and impaired removal of apoptotic cells could contribute to an overload of autoantigens (and in particular of nucleosomes) in circulation or in target tissues that could become available to initiate an autoimmune response. In susceptible individuals, this can lead to autoantibody-mediated tissue damage...

The initial novel observation of this study was that most B cells of male BXSB lupus mice bear surface IgG2a(b) of extrinsic origin. To define the surface antigen, we here examine three (NZBxBXSB)F1-derived IgG2a(b) monoclonal antibodies (mAbs) selected for binding to cell surfaces. Surprisingly, all three mAbs bound the nucleosome (nuc) particle, the fundamental unit of chromatin and an early target of autoimmunity in systemic lupus erythematosus. Their tentative dissociation constant (K(d)) for soluble nuc particles was approximately 7 x 10(-10) m...

Patients with primary antiphospholipid syndrome (PAPS) may evolve to systemic lupus erythematosus (SLE), even many years later. This makes differentiation between primary and secondary antiphospholipid syndrome a difficult task. Studies in murine models of lupus have shown that the development of antinucleosome (anti-NCS) antibodies may occur from the early stages of life. We therefore hypothesize that anti-NCS antibodies could help predict development of SLE in patients with PAPS. We studied anti-NCS antibodies in 18 PAPS patients (15 female, three male), followed for a mean of 11 years to evaluate the potential development of SLE...

We prospectively analyzed the diagnostic sensitivity and specificity as well as the clinical relevance of antinucleosome antibodies in SLE. One hundred and one consecutive SLE patients were followed for 3 years. Three serial serum samples from each patient were tested for antinucleosome antibodies by ELISA (optimum cut-off value 10 U/ml), and for anti-dsDNA antibody (by ELISA and IIF on Crithidia luciliae), and anti-dsDNA avidity (by Scatchard plot analysis). Sera from 100 healthy individuals (HI), 35 patients with systemic sclerosis (SSc), 30 with primary Sjögren's syndrome (SS), 20 with rheumatoid arthritis (RA) and 48 with infectious diseases (ID), were assayed as controls...

Two outstanding questions concerning antinuclear antibodies (ANAs) in lupus involve their pathogenic potential and their molecular signatures. To address these questions, a panel of 56 antinuclear and 47 nonnuclear binding monoclonal antibodies was rescued from four seropositive NZM2410 lupus mice. The monoclonals varied in their reactivity to nucleosomes, ssDNA, dsDNA, and glomerular substrate. A large fraction of the antibodies demonstrated apparent polyreactivity (to DNA, histones, and glomerular antigens) due to bound, DNase-1 sensitive nuclear antigenic bridges...

In lupus-prone NZM2328 mice, a locus Cgnz1 on chromosome 1 was linked to chronic glomerulonephritis, severe proteinuria, and early mortality in females. A locus Adnz1 on chromosome 4 was linked to antinuclear antibody (ANA) and anti-double stranded DNA (dsDNA) antibody (Ab) production. In this investigation, two congenic strains, NZM2328.C57L/Jc1 (NZM.C57Lc1) and NZM2328.C57L/Jc4 (NZM.C57Lc4), were generated by replacing the respective genetic intervals containing either Cgnz1 or Adnz1 with those from C57L/J, a nonlupus-prone strain...

The diagnosis of inflammatory joint disease rests on a constellation of symptoms, signs, laboratory test results and, occasionally, histological findings. Classification criteria have been developed by national learned societies, international panels of experts or, more rarely, an expert working alone. These criteria are intended to provide a common language for therapeutic trials and international publications. Yet, they are often inappropriately used as diagnostic tools for the individual patient. Identification of an early seroimmunologic marker with high sensitivity and specificity for classifying patients with recent-onset joint disease is a daunting challenge...

In the last decade it has become clear that systemic lupus erythematosus (SLE) is an autoantigen driven T cell dependent autoimmune disease. The nucleosome has been identified as a major autoantigen. Nucleosomes are generated during apoptosis. Either an increased or delayed apoptosis or a reduced clearance of apoptotic cells (which are not mutually exclusive) leads to an increased exposure of (modified, more immunogenic) nucleosomes to the immune system. This generates the formation of nucleosome specific T cells and antinucleosome autoantibodies...

OBJECTIVE: Antinuclear autoantibodies complexed to nucleosomes can bind to heparan sulfate (HS) in the glomerular basement membrane. This binding is due to the binding of the positively charged histones to the strongly anionic HS. Nucleosomes and histones have been identified in glomerular deposits in human lupus nephritis. We investigated whether nucleosomes are present in the basement membrane of nonlesional skin of lupus patients. METHODS: Skin biopsy samples from patients with systemic lupus erythematosus (SLE) (30 with active lupus nephritis and 15 with inactive disease) and controls (with parapemphigus or diabetes) were stained for IgG, histones, DNA, and nucleosomes...

Evidence is to date accumulating to suggest that the nucleosome, the fundamental unit of chromatin and ubiquitous product of cell apoptosis, plays a key role in the pathogeny of systemic lupus erythematosus (SLE). Nucleosomes play a central role in the antinuclear antibody response in SLE. Lupus anti-dsDNA and antihistone antibodies are directed towards nucleosomes and belong together with nucleosome-specific antibodies to a broad anti-nucleosome antibody family. Besides anti-dsDNA, nucleosome-specific antibodies have a major role in the pathophysiology of SLE and emphazise the role of nucleosome-antinucleosome immune complexes...

OBJECTIVE: To investigate the effect of infliximab treatment on antinuclear antibodies (ANAs), anti-double-stranded DNA (anti-dsDNA), antinucleosome, antihistone, and anti-extractable nuclear antigen (anti-ENA) antibodies in rheumatoid arthritis (RA) and spondylarthropathy (SpA) patients. METHODS: Sera from 62 RA and 35 SpA patients treated with infliximab were tested at baseline and week 30 (RA group) or week 34 (SpA group). ANAs were tested by indirect immunofluorescence (IIF) on HEp-2 cells...

OBJECTIVE: To evaluate the correlation between antinucleosome antibodies and disease activity in patients with systemic lupus erythematosus (SLE). METHODS: We evaluated antinucleosome antibodies (by ELISA) in 48 SLE patients. They were divided in 2 groups: positive (Group A, nr = 18) and negative (Group B, nr=30). The groups were evaluated for antinucleosome antibodies and for clinical, humoral parameters (hemoglobin, blood cell count, urinanalysis, ESR, ANA, anti-dsDNA, anticardiolipin antibodies, LAC), and ECLAM...

The objective of this study was to assess the utility of measurement of thrombomodulin, antinucleosome antibodies, sVCAM-1, sICAM-1, neopterin, fas ligand, IL-10 and sIL-2R in patients with systemic lupus erythematosus (SLE) and to compare them with traditional markers of SLE activity (anti-dsDNA antibodies, C3, C4) and the ECLAM index of disease activity. The measurement was performed over a 6-month period at three consecutive time points after 3 months in each of the 52 patients with SLE. Anti-dsDNA antibodies, thrombomodulin, antinucleosome antibodies, sVCAM-1m sICAM-1, neopterin, fas ligand, IL-10 and sIL-2R were tested by ELISA technique, while C3, C4 components of complement were tested by nephelometry...

OBJECTIVE: To evaluate the effect of disease progression and lipopolysaccharide (LPS) administration on the presence of nucleosomes, antinucleosome reactivity, and nucleosome-Ig complexes in the circulation of MRL and control mice. METHODS: Plasma samples from lupus-prone (MRL/lpr and MRL/+) and control (CBA, Swiss, and BALB/c) mice were tested in enzyme-linked immunosorbent assays for the presence of nucleosomes, antinucleosome antibodies, and nucleosome-Ig complexes...